The cyclic AMP receptor protein (CRP) is a DNA binding protein from Escherichia coli that can activate or repress transcription depending upon where it binds relative to a promoter. CRP serves as a model system for the study of gene control because it has provided a wealth of genetic and biochemical information about how positive control works. We have been studying the mechanism for how CRP activates transcription. (i) We have found that for CRP to activate transcription at the lac operon the structural integrity of the DNA is important. We have studied the spacer DNA between where CRP is bound and the lac promoter, and found that disruptions in this region such as single- stranded gaps or mismatches prevent CRP from activating transcription. We have also found that the sequence of the spacer region is unimportant for CRP-mediated transcription activation. (ii) We have identified genetically other factors that are involved in CRP activation of transcription in vivo.